This is the continuation of a long-term project designed to gain fundamental information about the mechanisms of action of purine and pyrimidine analogs and about the enzymes with which these analogs or their derivatives interact. Studies on the pathways of polyphosphate nucleotide synthesis and degradation: Currently under investigation is erythrocytic adenosine deaminase. The effect of tight-binding inhibitors, such as coformycin, will be studied with the isolated enzyme and in intact erythrocytes. Studies will continue on ADAase-deficient erythrocytes from patients with Severe Combined Immunodeficiency Disease (SCID). Studies on the mechanism of cytolytic action of purine and purine ribonucleoside analogs: Extensive studies have been performed on the incorporation of analog nucleosides into human erythrocytes and blood platelets, and similar studies have been initiated with peripheral lymphocytes. These studies will be extended to lymphocytes from patients treated with Imuran to various leukemic cells and to frozen lymphocytes. We also plan similar investigations with isolated granulocytes. Comparative studies on erythrocytic purine metabolism: A comparison of the enzymes of purine nucleotide metabolism of erythrocytes from humans, dogs, mice, rats, rabbits, hamsters, guinea pigs and pigs is under way. Highly significant differences have been detected which may have very important implications in experimental cancer chemotherapy. Human erythrocytes form nucleotides from guanosine and analogs such as 6-thioguanosine much more rapidly than do dog, mouse or rat erythrocytes. BIBLIOGRAPHIC REFERENCES: Adenosine Deaminase from Human erythrocytes: Purification and Effects of Adenosine Analogs: R. P. Agarwal, Stephen M. Sagar and R. E. Parks, Jr. Biochem. Pharmacol. 24, 693 (1975). Incorporation of the Purine Moieties of Guanosine and Inosine Analogs into Nucleotide Pools of Human Erythrocytes: Chong M. Kong and R. E. Parks, Jr. Biochem. Pharmacol. 24, 807 (1975).